Inclusion and Exclusion Criteria of Clinical Trials for Insomnia.

Hendrikje Huls,Joris Verster,Timothy Roehrs,Aurora Van De Loo,Thomas Roth,Smedra Abdulahad,Marlou Mackus

doi:10.3390/jcm7080206

Abstract

Randomized controlled trials (RCTs) have eligibility criteria for the inclusion of participants. Ideally, the RCT sample would be representative for the patient population that will use the drug under investigation. However, external validity may be at stake when applying too many or too restrictive eligibility criteria. The current two-part study examined (1) the currently applied eligibility criteria in Phase II and III RCTs examining sleep medication; (2) how these criteria match with the insomnia population as a whole; and (3) how inclusion rates can be changed by an adaptation of these criteria. In the first study, insomnia RCTs were screened at www.clinicaltrials.gov, and relevant eligibility criteria were identified. The second study comprised a survey among self-reported insomnia patients. It was determined to what extent RCT eligibility criteria match the characteristics of this patient population. Of the n = 519 patients that completed the survey only n = 2 (0.4%) met all eligibility criteria of current RCTs. RCT enrolment criteria are not representative for the insomnia patient population as a whole. Being less rigorous in applying upper or lower criteria limits results in a significant increase in the number of eligible patients, and increases the representativeness of RCTs for the insomnia patient population as a whole. The current analysis demonstrates that is important to thoroughly reconsider the use eligibility criteria and their inclusion ranges, and to have a theoretical basis for using them.

Highlights

Research of the safety and efficacy of new medicinal drugs is usually conducted via randomized controlled trials (RCTs) [1]
One of the aims of the current paper was to open the discussion among sleep specialists and RCT designers about the implications of applying specific eligibility criteria, to thoroughly think about these criteria, and to have a theoretical basis for using them
Research into enrolment criteria is very limited and the consequences of proposed eligibility criteria for inclusion rates of RCTs are often not appreciated by people who design RCTs

Summary

Introduction

Research of the safety and efficacy of new medicinal drugs is usually conducted via randomized controlled trials (RCTs) [1]. For strongly justified reasons a specific rationale can be provided, whereas this is less or not the case for potentially and poorly justified reasons, respectively This categorization can be applied to eligibility criteria of all RCTs, independent of the disease under investigation. If eligibility criteria are too specific, there is a risk of the research not being representative for the population of potential drug users This selection bias can cause unexpected events when a drug is brought on the market and will be used by the insomnia population at large that does not meet the strict RCT criteria. Post marketing data can identify potential risk factors, but it would be more ideal to identify these during drug development For this reason, RCT selection criteria must be cautiously chosen and strongly justified.

Online Survey

Statistical Analysis

Limitations

Findings

Conclusions